Biased immunoglobulin variable region gene expression by Ly‐1 B cells due to clonal selection

Abstract

Most, if not all, autoantibodies specific for bromelain‐treated mouse erythrocytes recognize the common membrane phospholipid, phosphatidyl choline (PtC). Anti‐PtC antibodies are produced by 5%‐15% of CD5⁺ Ly‐1 B cells of normal unimmunized mice, but not by detectable numbers of conventional CD5^– B cells. At 1 week of age PtC‐specific B cells are undetectable but then increase dramatically over the next 3 to 4 weeks to reach adult numbers. We report here that PtC‐specific Ly‐1 B cells in B10.H‐2^aH‐4^bp/Wts mice predominantly express either of two heavy and χ chain variable (V) region gene combinations. In addition, the sequence and length of D_H genes are conserved among cells expressing the same V gene combination, and the V_χ‐J_χ junctions of one group involve unusual splice sites. Preferential V gene rearrangement models are insufficient to explain the D_H and V_χ‐J_χ junctional sequences or the delayed appearance of this specificity, and so they cannot solely account for the high frequency of PtC‐specific cells. These characteristics are more consistent with antigen selection. We therefore attribute the frequent use of the two V region gene combinations to selection for cells that express them and conclude that the expressed V gene repertoire of Ly‐1 B cells in adult mice is influenced by antigen selection. Apparently, there is no selection for mutant anti‐PtC antibodies of higher affinity during the formation of the Ly‐1 B repertoire because the V region genes expressed by PtC‐specific cells are unmutated. Our findings are consistent with an important, germ line‐encoded function for the immunoglobulin products of these gene combinations.